Systems and methods for detecting a liquid level

ABSTRACT

A method for detecting a liquid surface of a liquid sample with a pipetting tip, the method includes receiving an indication of a capacitance of the pipetting tip, and determining, based on a rate of change of the indication of the capacitance rising above a first preselected threshold, that the pipetting tip has come into contact with the liquid surface. The method also includes determining, based on the rate of change of the indication of the capacitance falling below a second preselected threshold, that the pipetting tip has lost contact with the liquid surface.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. non-provisional patentapplication Ser. No. 15/352,281 filed Nov. 15, 2016, entitled “Systemsand Methods for Detecting a Liquid Level”, which claims benefit of U.S.provisional patent application No. 62/257,073 filed Nov. 18, 2015,entitled “Systems and Methods for Detecting a Liquid Level”, all ofwhich are hereby incorporated herein by reference in their entirety forall purposes.

BACKGROUND

Processing of liquids, such as aspiration and dispensation, is carriedout in a variety of contexts. For example, in a laboratory setting, arobotic device may aspirate and dispense liquids using apositive-displacement pump and associated pipette tip in order to carryout a variety of laboratory tasks, such as titration for performing aDNA assay. In such settings, it may be advantageous to detect when thepipette tip comes into and out of contact with the liquid beingaspirated or dispensed. However, conventional liquid level detectionmethods and apparatuses suffer from a lack of sensitivity, which canresult in inaccuracies when aspirating and dispensing small volumes(e.g., microliters) of liquid, a poor ability to accurately confirmwhether the pipette tip has fallen out of the liquid during aspiration,and/or a poor ability to confirm that the proper downward motion of thepipette tip has occurred to compensate for a height reduction of aliquid sample resulting from a previous aspiration.

BRIEF DESCRIPTION OF THE DRAWINGS

For a detailed description of exemplary embodiments of the disclosure,reference will now be made to the accompanying drawings in which:

FIG. 1 shows a block diagram of a system to detect a liquid surfaceusing a capacitance-based measurement and determination in accordancewith various embodiments of the present disclosure;

FIG. 2 shows an exemplary change in capacitance curve as a function oftime to illustrate the function of the system of FIG. 1 in accordancewith various embodiments of the present disclosure.

FIG. 3 shows a block diagram of a system to detect a liquid surfaceusing a pressure-based measurement and determination in accordance withvarious embodiments of the present disclosure;

FIGS. 4 and 5 show exemplary pressure curves as a function of time toillustrate the function of the system of FIG. 3 in accordance withvarious embodiments of the present disclosure;

FIG. 6 shows a flow chart of a method in accordance with an embodiment;

FIG. 7 shows a flowchart of a method in accordance with an embodiment;

FIG. 8 shows a flowchart of a method in accordance with an embodiment.

NOTATION AND NOMENCLATURE

Certain terms are used throughout the following description and claimsto refer to particular system components. As one skilled in the art willappreciate, companies may refer to a component by different names. Thisdocument does not intend to distinguish between components that differin name but not function. In the following discussion and in the claims,the terms “including” and “comprising” are used in an open-endedfashion, and thus should be interpreted to mean “including, but notlimited to . . . .” Also, the term “couple” or “couples” is intended tomean either an indirect or direct electrical connection. Thus, if afirst device couples to a second device, that connection may be througha direct electrical connection, or through an indirect electricalconnection via other devices and connections.

DETAILED DESCRIPTION

The following discussion is directed to various embodiments of thedisclosure. Although one or more of these embodiments may be preferred,the embodiments disclosed should not be interpreted, or otherwise used,as limiting the scope of the disclosure, including the claims. Inaddition, one skilled in the art will understand that the followingdescription has broad application, and the discussion of any embodimentis meant only to be exemplary of that embodiment, and not intended tointimate that the scope of the disclosure, including the claims, islimited to that embodiment.

As explained above, conventional liquid level detection methods andapparatuses suffer from a lack of sensitivity, which results in lessthan ideal performance in a number of scenarios. One reason for the lackof sensitivity stems from designs that rely heavily on analog signalprocessing for detecting and processing various signals related toliquid level sensing, such as capacitance and pressure or vacuum.Embodiments of the present disclosure address these and othershortcomings, resulting in a systems and methods for detecting a liquidlevel that are more accurate, capable of resolving anomalies in thepipetting process (e.g., clotting, bubble formation, foaming, and thelike), and generally more robust in laboratory environments wherevariables such as container size, liquid type, and other parameters maychange over time and without being known to the associated liquidprocessing hardware and software.

This disclosure is generally directed to methods for detecting a liquidsurface of a liquid sample with a pipetting tip coupled to a positivedisplacement pump. Certain examples utilize capacitance-baseddeterminations, while other examples utilize pressure (or vacuum)-baseddeterminations. Generally, examples of the present disclosure will bedescribed with reference to a pump mounted to a robotic arm controlledby associated control hardware and/or software. However, it should beappreciated that liquid level detection methods disclosed herein may beapplicable in a variety of fields outside of laboratory robotics.

For capacitance-based determinations, the pipetting tip is conductiveand is part of a circuit that measures capacitance. When the pipettingtip contacts a liquid in a container (e.g., a microtiter plate), anear-instantaneous increase in the capacitance is observed, which may beprocessed to determine a position of the liquid surface in relation tothe range of motion of the robotic arm supporting the pump, for example.

Similarly, when the pipetting tip is drawn out of the liquid (or whenthe liquid level falls below the pipetting tip due to the downwardmotion of the robotic arm being insufficient to maintain contact withthe liquid), a near-instantaneous decrease in the capacitance isobserved, which may be processed to determine a position or an updatedposition of the liquid surface in relation to the range of motion of therobotic arm. Further, in certain contexts, a determination that thepipetting tip has lost contact with the liquid when it was not expectedto do so may result in a change in one or more operational parameters ofthe robotic control or pump control systems, which will be explained infurther detail below.

For pressure-based determinations, a pressure transducer is coupled tothe working airspace of the pump (e.g., a cylinder whose volume changesas a result of displacement of a piston into and out of the cylinder) todetect a pressure of the airspace, which is coupled to the airspace inthe pipetting tip. As the pipetting tip is moved toward a liquidsurface, the pump controller causes the pump to begin aspirating air,resulting in a slight vacuum in the pipetting tip and associatedairspace, which is detected by the pressure transducer. When thepipetting tip contacts a liquid in a container (e.g., a microtiterplate), a near-instantaneous increase in the vacuum (or a correspondingdecrease in measured pressure) is observed, which may be processed todetermine a position of the liquid surface in relation to the range ofmotion of the robotic arm supporting the pump, for example. Although avolume of liquid may be aspirated before the vacuum change is detected,in many applications the volume may be quite minimal (e.g., severalmicroliters) and thus insignificant to an overall sample volume to becollected.

Similarly, when the pipetting tip is drawn out of the liquid (or whenthe liquid level falls below the pipetting tip due to the downwardmotion of the robotic arm being insufficient to maintain contact withthe liquid), a near-instantaneous decrease in vacuum (or a correspondingincrease in measured pressure, resulting from the inflow of atmosphericpressure air to the airspace) is observed, which may be processed todetermine a position or an updated position of the liquid surface inrelation to the range of motion of the robotic arm. Further, in certaincontexts, a determination that the pipetting tip has fallen out ofcontact with the liquid when it was not expected to do so may result ina change in one or more operational parameters of the robotic control orpump control systems, which will be explained in further detail below.

In both capacitance- and pressure-based determinations, a rate of changeof the capacitance and pressure may be compared to a threshold rate ofchange to determine whether a liquid surface has been contacted. Thatis, a rate of change in pressure or capacitance above the thresholdcorresponds to contacting the liquid surface, while a rate of change inpressure or capacitance below the threshold may correspond to ananomalous measurement, a measurement influenced by an external,non-liquid surface-related factor (e.g., capacitance of nearby bodiesinfluencing the capacitance seen at the pipetting tip, and the like. Asimilar rate of change-based analysis may be performed to detect thepipetting tip no longer contacting the liquid, where a rate of changebelow a negative threshold indicates that the pipetting tip has fallenout of contact with the liquid surface.

Turning now to FIG. 1 , a system 100 to detect a liquid surface using acapacitance-based measurement and determination is shown in accordancewith various embodiments. The system 100 includes a probe 102, such as apipette tip; however, in certain embodiments a capacitively-coupledprobe 102 may be used in conjunction with a traditional pipette tip,which is not shown for simplicity. The probe 102 is a conductive probethat is isolated from ground, and is attached to a circuit that measurescapacitance seen by the probe 102 as explained in further detail below.

A capacitance to pulse width generator 104 logic block generates a pulsehaving a width related to the value of capacitance sensed from the probe102. That is, the pulse width generator 104 generates a pulse whose timeduration is proportional to the capacitance measured by the probe 102.Stated otherwise, a capacitance to pulse width generator 104 isconfigured to output a pulse having a width based on a capacitance seenby the pipette probe. As will be explained in further detail below, incertain embodiments of the present disclosure an absolute capacitancevalue is not particularly important, but rather a determination is madebased on a perceived rate of change of the capacitance value indicatedby the pulse generated by the pulse width generator 104. In certainother embodiments, the system 100 may be calibrated such that theabsolute value of capacitance sensed from the probe 102 and indicated bythe pulse width generator 104 is leveraged instead of or in addition tothe rate of change of capacitance in order to provide further accuracyin detecting a liquid surface.

The output of the pulse width generator 104 is provided to a digitalsignal processor (DSP) 106 and, in particular, a period measurementblock 108 of the DSP 106. DSP 106 is configured to compare a signalbased on the width of the pulse with a preselected positive thresholdand a preselected negative threshold, as described further below. In atleast some embodiments, the period measurement block 108 gates anoscillator (not shown) of the DSP 106 in response to receiving a pulsefrom the pulse width generator 104 and counts the number of oscillatorcycles that occur during the duration of receiving the pulse from thepulse width generator 104. The number of oscillator cycles countedindicates a relative value of capacitance or, in embodiments where thesystem is so calibrated, may indicate an absolute value of capacitanceseen by the probe 102.

The DSP 106 also includes a frequency generator 107, which may dividedown the oscillator signal generated by the DSP 106 (e.g., a 30-60 MHzsignal) to a frequency more appropriate for the capacitance to pulsewidth generator 104 (e.g., 40 kHz). The signal provided by the frequencygenerator 107 is used to trigger a oneshot in the pulse width generator104. An output period of the oneshot varies as a function of thecapacitance of the probe 102 and whatever the probe 102 is in contactwith. As described above, the output period of the oneshot is measuredby the gated timer of the period measurement block 108. Statedotherwise, the output period of a capacitance to pulse width generator104 is based on the capacitance seen by the pipette probe, and theperiod measurement block 108 is configured to measure the output periodof the a capacitance to pulse width generator.

The DSP 106 also includes a low pass filter 110 that receives the“count” or indication of pulse duration from the period measurementblock 108. In certain embodiments, the low pass filter 110 may comprisea 3^(rd)-order infinite impulse response (IIR) filter. The filter 110reduces noise components of the signal generated by the periodmeasurement block 108. In particular, because the values of capacitancebeing sensed by the probe 102 may be very small, the signal output bythe period measurement block 108 may include large amounts ofhigh-frequency noise (i.e., the signal-to-noise ratio (SNR) of theoutput of block 108 may be expected to be poor). Thus, the filter 110reduces the high-frequency noise generated by block 108 to produce arelatively clean, noise-reduced signal.

The noise-reduced output of the filter 110 is provided to adiscriminator block 112, which identifies sudden positive or negativeslope changes (i.e., rates of change above or below certain, preselectedthresholds). Stated otherwise, a discriminator 112 may be configured toidentify a change in slope in the signal based on the width of the pulsefrom a capacitance to pulse width generator 104 and generate a signalhaving a magnitude based on the change in slope. In some embodiments,the discriminator block 112 may comprise a 20^(th) order finite impulseresponse (FIR) filter, which discriminates the sudden changes from abackground signal. When the probe 102 contacts a liquid surface, a largepulse is generated by the low pass filter 110 and discriminator 112.Conversely, when the probe 102 falls out of contact with a liquid, asimilarly-large but opposite-sign pulse is generated by the low passfilter 110 and discriminator 112 (FIG. 2 ).

The DSP 106 may compare a magnitude of the pulse generated by thediscriminator 112 to a threshold 114, 115 to determine whether the pulseis to be interpreted as contacting (or losing contact with) a liquidsurface. In other words, a positive threshold detector 114 may comparethe magnitude of the signal from a discriminator 112 having a positivesign with the preselected positive threshold, and a negative thresholddetector 115 may compare the magnitude of the signal from adiscriminator 112 having a negative sign with the preselected negativethreshold. In other embodiments, the DSP 106 may compare a rate ofchange of the pulse generated by the discriminator 112 to a threshold todetermine whether the rate of change of the pulse is to be interpretedas contacting (or losing contact with) a liquid surface. Advantageously,the threshold may be set at a point between the peak value of the noise(i.e., so noise present in the discriminator 112 output does not triggera detection) and the peak value of the discriminator 112 output whencontacting (or losing contact with) a liquid surface.

In certain embodiments, the DSP 106 may “stretch” the threshold detector114, 115 output(s) after comparing it to a threshold to avoid potentialdifficulties associated with identifying a very narrow (i.e., transient)signal pulse for subsequent use as to whether the probe 102 hascontacted or fallen out of contact with a liquid surface. It should beappreciated that various ones of the described components of the system100 may have their circuitry and/or component values adjusted to provideappropriate resolution and dynamic range for the particular system 100requirements and operating environment context.

Ultimately, detected outputs 116, 117, which may indicate whether theprobe 102 has contacted or fallen out of contact with a liquid surface,may be provided to various other control circuitry or mechanisms,including hardware, software, and/or combinations thereof. These controlmechanisms will be described in further detail below. Further, it shouldbe appreciated that although the detected outputs 116, 117 are shown asseparate outputs, the actual output of the DSP 106 may comprise a serialdata output that indicates both of the detected outputs 116, 117.

FIG. 2 shows an example graph 200 of relative change in capacitance (inarbitrary units) as a function of time. A response 202 (i.e., a pulsegenerated by the discriminator 112) occurs when the pipetting tip 102contacts a liquid surface. Similarly, a response 204 (i.e., anopposite-sign pulse generated by the discriminator 112) reflects thechange in capacitance reaction when the pipetting tip 102 comes out ofcontact with the liquid surface. It is noted that noise components ofthe output of the discriminator 112 become worse between pulses 202, 204because capacitance sensed while the probe 102 is in the liquid is alarger value, and thus more variation is introduced into the signalsinput to the discriminator 112. Noise regions 206 and 210, and thepositive and negative peak values 208, 212 of pulses 202 and 204respectively are described further in conjunction with FIG. 8 .

Turning now to FIG. 3 , a system 300 to detect a liquid surface using apressure-based measurement and determination is shown in accordance withvarious embodiments. The system 300 is generally similar to the system100 that relies upon a capacitance-based measurement and determination.Of course, rather than a conductive probe 102, the system 300 includes apressure transducer 302. The pressure transducer 302 generates an outputsignal related to a pressure values (or vacuum value) sensed by thepressure transducer 302. The pressure transducer 302 may be positionedin fluid communication with a working airspace of a pump, such as a pumpcylinder, which is also in fluid communication with the interior volumeof a pipette tip when coupled to the pump. Advantages may be realized byreducing the total volume of air the pressure transducer 302 is incommunication with, which may result in an increase in precision and/oraccuracy of the signal generated by the pressure transducer 302.

The system 300 includes a DSP 304 similar to the system 100 describedabove in FIG. 1 . The pressure transducer 302 may be coupled to the DSP304 wherein the DSP 104 may be configured to output a signal having anamplitude based on a rate of change of a pressure in the interior volumeof the pipette tip, as described further below. The DSP 304 includes ananalog-to-digital converter (ADC) 304, a low pass filter 308, and adiscriminator 310 and detectors 312, which are similar in function totheir counterparts described above with regard to FIG. 1 . In at leastsome embodiments, the discriminator 310 may be coupled to an output ofan ADC 304 via a low pass filter 308, and be configured to output asignal having a magnitude based on a magnitude of the rate of change ofthe pressure in the interior volume of the pipette tip. The outputsignal of the discriminator 310 may have a sign based on the sign of therate of change of the pressure in the interior volume, e.g. a positivesignal for a positive rate of change, and vice versa. Similar tothreshold detectors 114, 115, FIG. 1 , the output signal of thediscriminator 310 may be coupled to detectors 312, wherein the detectors312 are configured to compare the output signal of the discriminator 310having a positive sign with a preselected positive threshold and theoutput signal having a negative sign with a preselected negativethreshold.

As will be appreciated, a pressure-based determination as in FIG. 3 isbetter suited for use while actively pipetting (i.e., operating the pumpto aspirate or dispense from the pipette tip, even if only air). Forexample, when contacting a liquid surface while aspirating through thepipette tip, an increased change in pressure detected (and thus a moreappreciable rate of change of pressure) is observed, which results ineasier subsequent detection. However, capacitance-based determinationsare not reliant on whether pipetting is occurring, and thus may beutilized in a potentially-wider variety of contexts. Pressure-baseddeterminations have the advantage of not requiring a conductivepipetting tip, however.

Further, pressure-based determinations may provide advantages overcapacitive-based determinations when detecting foam or clottingconditions, which capacitance does not effectively discriminate against.For example if foam is on the surface of sample is contacted by thecapacitance probe, it cannot effectively differentiate that contact fromcontacting the surface. In the case of pressure, if during aspirationthere is foam on the surface of the liquid sample there will be suddenchanges in pressure while trying to aspirate the foam that can be usedto indicate that the sample has foam on its surface and accuratepipetting may not be possible. Similarly, if during aspiration a clot isaspirated and it blocks flow in the tip, vacuum will increase by morethan an expected, or predetermined, amount and a clogged pipettercondition can be detected.

Further, in certain embodiments, knowledge of properties of the liquidbeing aspirated may be leveraged to improve clotting and/or foamdetection. For example, the system 300 may be improved by utilizingknowledge regarding liquid viscosity, density, and the like and possiblyapplying different sets of parameters and/or thresholds for each variousliquid being handled. In other embodiments, an expected pressure valuemay be correlated to a rate of aspiration (e.g., using a lookup table orequation) such that if an observed pressure deviates from an expected,or predetermined, pressure for a given rate of aspiration, then foaming,clotting, short sampling, or other anomalous condition may be detected.The lookup table or equation may also take into account the pipette tipinner diameter, which varies by pipette size (volume).

FIG. 4 shows an exemplary relative pressure (in arbitrary units) curve400 as a function of time, which demonstrates various events that may bedetected using a pressure-based determination, explained above. Thefollowing discussion refers to aspects of the pressure curve 400 inchronological order.

The pressure curve 400 includes signal 402 where the liquid surface iscontacted as the pipetter is moved toward the surface while the pipetteris aspirating. The pressure curve 400 also includes a time at which apre-selected vacuum threshold 404 is set. At this time, the relativelocation of the surface is established by noting the position of thepipetter at that time and the aspiration stops.

Subsequently, the pressure curve 400, at 406, reflects the pipette tip102, FIG. 1 , coming out of contact with the liquid. The pressure curve400 trends upward at 408 while dispensing liquid and air aspiratedduring the liquid level detecting operation. Then, as an air gap isaspirated to allow subsequent full dispensing of the sample volume, thepressure curve 400 falls sharply, at 410, due to a vacuum being pulledin the working airspace of the pump. Finally, when aspirating a liquidsample, the vacuum pulled is even sharper, resulting in a morepronounced decrease in the pressure curve 400, at 412.

FIG. 5 shows an exemplary graph 500 demonstrating pressure readings aswell as a rate of change of vacuum as a function of time, whichparticularly represents the identification of a short sample using apressure-based determination. Curve 502 (solid line) on the graph 500shows the relative pressure (in counts, on the vertical axis) versustime (on the horizontal axis) during aspiration of a sample withpipetter robot speed reduced to force a short aspiration or sample(i.e., where the pipette tip loses contact with the liquid duringaspiration). The rate of change of the vacuum is plotted in curve 504(dashed line). Thus a decrease in pressure is an increase in vacuum andthus corresponds to a positive rate-of-change of vacuum, and vice versa.In this example graph 500, the desired aspiration time is 0.4 seconds.The pressure initially reduces rapidly, at 506, and then more gradually,at 508, until the pipette tip pulls out from the liquid, atapproximately 0.35 seconds. These correspond to regions 507 and 509 incurve 504. At this time the pressure rises rapidly, region 510 in curve502, corresponding to dip 511 in curve 504, and can be used to determinethat an incomplete aspiration has occurred, as the full desiredaspiration time of 0.4 seconds was not reached before it is determinedthat the pipette tip lost contact with the liquid. Similarly the rate ofchange of vacuum can be used to make this determination by comparing thevalue in the dip 511 to a predetermined threshold.

Certain embodiments of the present disclosure may use bothpressure-based and capacitance-based determinations in tandem, in orderto provide advantages associated with each type of determination.Further, as indicated above, a detected output 116, 117 may indicatewhether the probe 102 has contacted or fallen out of contact with aliquid surface. Subsequent control mechanisms may incorporate variousalgorithms to detect and address issues associated with differentcontainer or vessel sizes.

For example, in the event a system 100, 300 has been incorrectlyprogrammed to work with a certain container size in a particular fluidprocessing step, embodiments of the present disclosure may identify theincorrect container size and cause the control mechanisms to update acontainer size. For example, if it is determined that the pipette tiphas fallen out of a liquid before it should have (e.g., the robotic armis not moving down fast enough for the rate of aspiration due to anunderestimation of container size), or that the pipette tip remains incontact with the liquid when it should have fallen out (e.g., therobotic arm is not moving up as expected).

In either of these examples, the control mechanisms may update one ormore parameters associated with that particular step of the fluidprocessing, such as adjusting the container size, adjusting the rate ofmovement of the robotic arm during aspiration, and/or adjusting the rateof aspiration of the pump itself. Depending on the time available, andin the event of a short sample, the short sample may either be dispensedand a second aspiration attempt made (either with or without alteringparameters of that fluid processing step as described above) or a testassociated with that particular sample may be identified as deficient(e.g., the sample and the remainder of the fluid processing of thatsample is thrown away).

To ease calibration of the system 100, 300, a normal and shortaspiration cycle may be carried out while monitoring the level of outputfrom the discriminator 112, for example. Based on the output from thediscriminator during these cycles, signal processing parameters such asoptimum thresholds (e.g., rate of change of capacitance or pressure thatcorresponds to a known liquid surface contact or loss of contact event)may be determined for subsequent use to detect contact and loss ofcontact with a liquid surface. In this way, various systems 100, 300 maycompensate for slight unit-to-unit sensitivity variation due tomanufacturing tolerances, or variations due to working with liquidshaving different physical characteristics, and the like. This strategycan also be used to optimize performance for different liquid types thatneed to be aspirated by a pipetter on the same system, for example wherecertain characteristics differ between liquids used in different stagesof the laboratory process.

Embodiments of the present disclosure may also be directed to anon-transitory computer-readable medium. Such a computer-readable mediummay contain instructions that, when executed by a processor (e.g., DSP106, 304, or another microprocessor coupled thereto), cause theprocessor to carry out all or portions of the methods and processesdescribed herein.

Embodiments of the present disclosure provide a method of detecting aliquid surface as part of a pipetting sequence. This minimizes pipettetip wetting and improves precision and accuracy of the pipetting.Further, sensitivity and detection are improved to the point ofpermitting aspirating and dispensing of volumes in the low microliterrange. FIG. 6 shows a flowchart of a method for detecting a liquidsurface of a liquid sample with a pipetting tip, block 600. In block anindication of a capacitance of the pipetting tip is received. In block604 it is determined that the pipetting tip has come in contact with theliquid surface based on the rate of change of the indication of thecapacitance rising above a first preselected threshold value. In block606, it is determined that the pipetting tip has lost contact with theliquid surface based on the indication of the capacitance falling belowa second preselected threshold value. Thus In addition to detecting whencontact is made with the liquid surface, the method also detects when apipetting tip or probe has lost contact with the liquid, which may beleveraged to assure that the pipetting tip has not lost contact with theliquid while it is being aspirated, via a positive displacement pumpcoupled to the pipetting tip, for example (i.e., that a short samplecondition has not occurred). Stated otherwise, in response, duringaspiration of the liquid sample into the pipetting tip, to determiningthat the pipette tip has lost contact with the liquid surfaceprematurely, the liquid sample may be identified as a short sample. Inresponse to identifying the sample as a shot sample, a remedial actionmay be performed. Exemplary remedial actions include dispensing theshort sample and aspirating a second sample. Further example remedialactions comprise dispensing the short sample, altering one or moreparameters of positive displacement pump or a motion control apparatussuch as a robotic arm coupled to the positive-displacement pump andaspirating a second liquid sample into the pipetting tip using thealtered parameters, or alternatively, a test associated with the shortsample may be identified as deficient. Note further that this functionfurther provides a confirmation that the proper downward motion of thepipette tip has occurred to compensate for the height reduction of theliquid in the tube as it is being aspirated. Method 600 ends at block608.

FIG. 7 show a flowchart of a method for detecting a liquid surface of aliquid sample, block 700, the detecting with a pipetting tip coupled toa positive displacement pump having a pump chamber. In block 702, anindication of a vacuum of the pump chamber is received. An aspirationcycle is begun prior to the pipetting tip contacting the liquid surface,in block 704. In block 706, it is determined, based on a rate of changeof the indication of vacuum rising above a first preselected threshold,that the pipetting tip has contacted the liquid surface. In block 708,it is determined, based on a rate of change of the indication of vacuumfalling below a second preselected threshold, that the pipetting tip haslost contact with the liquid surface. Further, during aspiration of theliquid sample, a clotting condition and a foaming condition proximate tothe pipetting tip may be identified: the clotting condition may beidentified by the indication of vacuum increasing by more than a firstpredetermined amount. The foaming condition proximate to the pipettingtip may be identified by the indication of vacuum varying in time bymore than a second predetermined amount. In response to identifyingeither the clotting condition or the foaming condition, a remedialaction may be performed. Note, as described above, the first and secondpredetermined amounts may be based on a size of the pipetting tip,and/or rate of aspiration, for example.

As described above, a calibration may be performed to set thethresholds. FIG. 8 shows a flowchart of a method 800 which may be usedto set thresholds in accordance with an embodiment. Method 800 starts atblock 802. In block 804, a level sensing operation, as previouslydescribed, is initiated. During the level sensing operation, as thepipetting probe descends toward the surface of the fluid sample, a firstnoise level of an output of the discriminator, e.g. discriminator 112,FIG. 1 , is measured, in block 806. For example, referring to FIG. 2 ,in at least some embodiments, a root mean-square (RMS) value of thesignal in noise region 206 may be used to establish a positive thresholdvalue at a preselected multiple of the RMS noise, e.g. three times theRMS noise signal, to mitigate against false detection of the contact ofthe pipette probe with the surface of the fluid sample. In otherembodiments, a multiple of the positive peak noise value in the noiseregion 206 may be used as the preselected positive threshold. In stillother embodiments, the positive threshold may be set at the averagebetween the RMS value in region noise region 206 and the detectedpositive peak value 208 of pulse 202. In still other embodiments, thepositive threshold may be set at an average of the peak positive valuein the noise region 206 and the detected positive peak value 208 ofpulse 202. Further still, in some embodiments, a statistical measurementof the noise may be used, and the positive threshold may be set to apreselected multiple, for example, 5×, of the standard deviation of thefirst noise level of the output of the discriminator. In block 808, thepositive threshold is set based on the measured first noise level in theoutput of the discriminator, in block 806. The pipetting tip iswithdrawn during the level sensing operation, in block 810, and in block812, a second noise level of the discriminator output signal ismeasured. For example, the second noise level is measured in noiseregion 210, FIG. 2 . Similar to setting the positive threshold, in atleast some embodiments, a root mean-square (RMS) value of the signal innoise region 210 may be used to establish a negative threshold value ata preselected multiple of the RMS noise, e.g. three times the RMS noisesignal, to mitigate against false detection of the loss of contact ofthe pipette probe with the surface of the fluid sample. In otherembodiments, a multiple of the negative peak noise value in the secondnoise level may be used as the preselected negative threshold. In stillother embodiments, the negative threshold may be set at an average ofthe peak negative value in the noise region 210 and the detectednegative peak value 212 of pulse 204. In still other embodiments, thenegative threshold may be set at the average between the RMS value inregion noise region 210 and the detected negative peak value 212 ofpulse 204. Further still, in some embodiments, a statistical measurementof the noise may be used, and the negative threshold may be set to apreselected multiple, for example, similar to the positive thresholdcase, 5×, of the standard deviation of the second noise level of theoutput of the discriminator. In block 814 the preselected negativethreshold is set based on the measurement in block 812. Method 800 endsat block 816.

The above discussion is meant to be illustrative of the principles andvarious embodiments of the present disclosure. Numerous variations andmodifications will become apparent to those skilled in the art once theabove disclosure is fully appreciated. It is intended that the followingclaims be interpreted to embrace all such variations and modifications.

What is claimed is:
 1. A method for detecting a liquid surface of aliquid sample with a pipetting tip, the method comprising: receiving anindication of a capacitance of the pipetting tip coupled to a positivedisplacement pump; determining, based on a rate of change of theindication of the capacitance rising above a first preselectedthreshold, that the pipetting tip has come into contact with the liquidsurface; aspirating the liquid sample into the pipetting tip using apredetermined pump rate of the positive-displacement pump; determining,based on the rate of change of the indication of the capacitance fallingbelow a second preselected threshold, that the pipetting tip has lostcontact with the liquid surface; and in response to determining that thepipetting tip has fallen out of contact with the liquid surface, andbased on the predetermined pump rate, identifying a size of a containerholding the liquid sample.
 2. The method of claim 1 further comprising:aspirating the liquid sample into the pipetting tip; in response todetermining that the pipetting tip has lost contact with the liquidsurface prematurely, identifying the liquid sample as a short sample;and in response to identifying the liquid sample as a short sample,performing a remedial action.
 3. The method of claim 2 wherein theremedial action comprises one selected from the group consisting of:dispensing the short sample and aspirating a second sample; dispensingthe short sample, wherein the pipetting tip is coupled to a positivedisplacement pump and altering one or more parameters of thepositive-displacement pump or a motion-control apparatus coupled to thepositive-displacement pump, and aspirating a second liquid sample intothe pipetting tip using the altered parameters; and identifying a testassociated with the short sample as deficient.
 4. The method of claim 1,wherein the receiving comprises receiving a pulse having a width basedon the capacitance.
 5. The method of claim 4, wherein the determiningthat the pipetting tip has come into contact with the liquid surface andthe determining that the pipetting tip has lost contact with the liquidsurface each comprises comparing the width of the pulse with apreselected positive threshold and a preselected negative threshold.